Purpose
To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability.
Let’s keep up the good work for a prolific new year!
Abstract:
While T2-exchange (T2ex) NMR phenomena have been known for decades, only recently there has been a resurgence of interest to develop T2ex MRI contrast agents. One indispensable advantage of T2ex MR agents is the possibility of using non-toxic and/or bio-important diamagnetic compounds with intermediate exchangeable protons. In this study, we screened a library of phenol-based compounds and determined their T2ex contrast (exchange relaxivity, r2ex) at 9.4 T. Our results showed that the T2ex contrast of phenol protons allows them to be detected directly by MRI at a mM concentration level. We also studied the effect of chemical modification of the phenol on the T2ex MRI contrast through modulation of exchange rate and chemical shift. This study provides a guideline for using endogenous and exogenous phenols for T2ex MRI contrast. As a proof-of-principle application, we demonstrated phenol T2ex contrast can be used to detect enzyme activity in a tyrosinase-catalyzed catechol oxidation reaction.
Congrats to Jia for the new publication!
Safe imaging agents that are able to render the expression and distribution of cancer receptors, enzymes or other biomarkers would facilitate clinical screening of the disease. Here, we show that diamagnetic dextran particles that are coordinated to a urea-based targeting ligand for prostate-specific membrane antigen (PSMA) enable targeted magnetic resonance imaging (MRI) of the PSMA receptor. In a xenograft model of prostate cancer, micromolar concentrations of the dextran–ligand probe provided sufficient signal to specifically detect PSMA-expressing tumours via chemical exchange saturation transfer MRI. The dextran-based probe could be detected via the contrast that originated from dextran hydroxyl protons, thereby avoiding the need of chemical substitution for radioactive or metallic labeling. Because dextrans are currently used clinically, dextran-based contrast agents may help to extend receptor-targeted imaging to clinical MRI.
Congratulations to Guanshu for the new publication!
Full text of the publication can be found at:
https://www.nature.com/articles/s41551-017-0168-8
To investigate the use of natural dextrans as nano-sized chemical exchange saturation transfer (CEST) MRI probes for characterizing size-dependent tumor vascular permeability.
Dextrans of different molecular weight (10, 70, 150, and 2000 kD) were characterized for their CEST contrast. Mice (N = 5) bearing CT26 subcutaneous colon tumors were injected intravenously with 10 kD (D10, 6 nm) and 70 kD (D70, 12 nm) dextran at a dose of 375 mg/kg. The CEST-MRI signal in the tumors was assessed before and approximately 40 min after each injection using a dynamic CEST imaging scheme.
All dextrans of different molecular weights have a strong CEST signal with an apparent maximum of approximately 0.9 ppm. The detectability and effects of pH and saturation conditions (B1 and Tsat) were investigated. When applied to CT26 tumors, the injection of D10 could produce a significant “dexCEST” enhancement in the majority of the tumor area, whereas the injection of D70 only resulted in an increase in the tumor periphery. Quantitative analysis revealed the differential permeability of CT26 tumors to different size particles, which was validated by fluorescence imaging and immunohistochemistry.
As a first application, we used 10- and 70-kD dextrans to visualize the spatially variable, size-dependent permeability in the tumor, indicating that nano-sized dextrans can be used for characterizing tumor vascular permeability with dexCEST MRI and, potentially, for developing dextran-based theranostic drug delivery systems. Magn Reson Med, 2017. © 2017 International Society for Magnetic Resonance in Medicine.
For the full text, please use the following link: http://onlinelibrary.wiley.com/doi/10.1002/mrm.27014/full